Table 7.
Inhibition of Agonist-Stimulated [35S]GTPγS Binding in Cloned Human μ, δ, and κ Opioid Receptors, Comparison of Structural Changes in JDTic to Similar Changes in 12
 | |||||||
|---|---|---|---|---|---|---|---|
| compd | structure | R1, R2 |
Ke (nM)a |
μ/κ | δ/κ | ||
| μ, DAMGO | δ, DPDPE | κ, U69,593 | |||||
| JDTic | A | OH, H | 25 ± 0.01 | 74 ± 2 | 0.02 ± 0.01 | 1255 | 3800 |
| 12 | B | OH, H | 239 ± 22 | >3000 | 0.37 ± 0.09 | 645 | >8100 |
| 40b | A | CONH2, H | 7.09 ± 2.58 | 131 ± 23 | 0.02 ± 0.01 | 355 | 6550 |
| 41 | B | CONH2, H | 41.3 ± 11 | >3000 | 1.37 ± 0.32 | 30 | >2190 |
| 42b | A | OCH3, H | 51.4 ± 15 | 118 ± 45 | 0.06 ± 0. | 857 | 1970 |
| 43 | B | OCH3, H | 1200 ± 140 | >3000 | 25.6 ± 6.3 | 47 | >117 |
| 44b | A | F, H | 7.7 ± 0.9 | c | 2.20 ± 0.47 | 3.5 | |
| 45 | B | F, H | >3000 | >3000 | 182 ± 19 | >17 | >17 |
| 46d | A | OH, CH3 | 210 ± 60 | 491 ± 120 | 0.16 ± 0.06 | 1313 | 3070 |
| 47 | B | OH, CH3 | 752 ± 140 | >3000 | 36.7 ± 5.6 | 20 | >82 |
a
Data are mean ± SEM of at least three independent experiments conducted in duplicate.
b
Taken from ref 21.
c
This compound was an inverse agonist at the δ opioid receptor with an IC50 of 97 ± 7 nM and percent basal binding of 78 ± 3% (data are mean ± SEM of three independent experiments conducted in duplicate).
d
Taken from ref 25.